HIV-1 infectivity is highly dependent on the viral-encoded gene Virion Infectivity Factor (Vif). Vif has been implicated in HIV-1 infectivity based on the discovery of varied responses that different types of human cells have to HIV-1 lacking Vif. Some cell types infected with HIV-1 lacking Vif still produce infectious virus and are called permissive cell types. In other cell types, designated non-permissive, HIV-1 encoding Vif can produce infectious virus while HIV-1 lacking Vif cannot.
One protein, called “apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G” (APOBEC3G) (previously named Cem15), has been discovered that can cause cells to become immune to HIV-1 lacking Vif (i.e., they become non-permissive) (Madani and Kabat, J. Virol. 74:5982-5987(2000)). As a DNA editing enzyme, APOBEC3G severely mutates newly made viral cDNA, which is DNA synthesized from viral RNA during HIV-1 reverse transcription (Gu and Sundquist, Nature 424:21-22(2003)). In the absence of Vif, APOBEC3G is packaged with the virus and exerts its effect after the virus infects another host cell. Highly mutating viral cDNA during the early stages of reverse transcription leads to destruction of the HIV-1 genome and a detrimentally high mutation rate within genes encoded by the HIV-1 genome (Gu et al., supra). Thus, APOBEC3G has damaging effects on HIV-1 that are prevented by the presence of Vif during HIV-1 infection. Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3F (APOBEC3F) is closely related to APOBEC3G, and has also been shown to have antiretroviral activity in vitro (Cho et al., J Virol. 80(4):2069-2072 (2006)).